The overall objective of this proposal is to produce human monoclonal antibodies (HMabs) which react with envelope glycoproteins (gp120, gp41, gp160) of human immuno-deficiency virus type 2 (HIV-2). HMabs will be produced by EBV transformation of B cells from HIV-2 infected subjects, most of whom will be West Africans. We will determine whether HMabs react with conserved or variant epitopes and whether these epitopes are linear or conformation dependent. We will map the binding site of each HMab. The biological activity of each HMab will be determined with respect to virus neutralization, antibody dependent cell-mediated cytotoxicity, and antibody dependent enhancement of infectivity. It will be of particular interest to learn whether sites of HIV-2 gp120 which are involved in neutralization are the same as or different from the major targets neutralization in HIV-1. Results of these studies should improve our understanding of HIV-2 pathogenesis, particularly with regard to humoral immune factors which may explain why the incubation period for HIV-2 disease is much longer than for HIV-1 disease. In addition, we may be able to identify epitopes that account for cross- reactivity in envelope antigens of HIV-1 and HIV-2.